Oct- 27, 1923 
Otocephaly in Guinea Pigs 
177 
In looking for nongenetic factors peculiar to individuals of a litter, 
acting very early in development and not affecting to an important 
extent the final growth of the body, we are led at once to a factor which 
Mall 5 considered important, a delayed or temporarily faulty implan¬ 
tation. Since neither the condition of the dam nor the heredity of the 
young (within the line) is of prime importance, we must attribute such 
errors in implantation largely to chance. We must assume that normal 
relations are later established, but only after irreparable injury has 
been done to the most sensitive region in the developing embryo, which, 
according to Child's gradient hypothesis, should be at the anterior end 
of the central nervous system. 
The minor grades of defect (grades 1 to 4) in which all the abnormali¬ 
ties seem to center around reduction of Meckel's cartilage (and to a less 
extent the hyoid) at first sight seem at variance with this theory, since 
Meckel’s cartilage would hardly seem a likely location for the highest 
and most sensitive point in the gradient pattern. It has been demon¬ 
strated, however, that the branchial cartilages are produced from mesecto- 
derm cells which wander down from the neural crest (6, 10 ) (Miss Platt, 
1897; Stone, 1922). A temporary arrest of development of the anterior 
end of the medullary plate might well cause a disturbance in the neural 
crest region, with consequences visible in the branchial cartilages even 
though not obvious in the brain. The arrest of the frontonasal process 
indicated in grade 5 leads to the series of stages (grades 6 to 12) in which 
the increasing arrest of the brain, beginning with the forebrain, is ob¬ 
viously the primary morphological factor. 
GENERAL CONSIDERATIONS 
Most work in genetics has necessarily dealt with variations of a rather 
superficial character whose relation to the great stream of heredity which 
determines the characteristics of the phylum, class, down even to the 
species, is like that of the ripples on the surface of a great river. One's 
impression on seeing a cyclopean in a litter of normal guinea pigs is that 
here is a variation of a more fundamental character, one which alters the 
entire course of development. At first thought it is somewhat discon¬ 
certing to this idea to find that the action of the hereditary factors in 
this case is so general in character that it is duplicated by that produced 
by a host of other agents, as cold, magnesium salts, butyric acid, me¬ 
chanical destruction, lack of oxygen, in short anything which arrests 
development. The only thing that seems to be specific is the moment 
in development in which the agent is in action. The genetic factors 
which render individuals of Family 13 especially likely to follow the 
otocephalic mode of development appear, then, to be factors which alter 
the metabolic activities of the embryo at a critical time in development 
causing it to be unusually susceptible to inhibiting agents, among which 
the consequences of chance irregularities in implantation appear to be 
most important. That these genetic factors themselves do not tend to 
determine faulty implantation is indicated by the failure of Family 13 to 
6 Mall ( 4 , 5), however, considered cyclopia as wholly nongenetic. He drew a rather sharp line between 
a class of anomalies such as polydactyly, which he considered as wholly germinal, and real monsters, in¬ 
cluding cyclopia, clubfoot, anencephaly, spina bifida, etc., which he considered as wholly pathological,. 
Wilder (ij) also drew a line between germinal and pathological monsters, but a different line. He included 
cyclopia among the orderly symmetrical beings, “cosmobia,” which he considered as germinal. The 
present data indicate that no sharp line can be drawn. Both germinal and environmental conditions 
play a part in determining cyclopia, and the same is undoubtedly true of other anomalies, including 
polydactyly and even variations in the piebald and tortoise-shell-color patterns in guinea pigs. 
